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https://www.readbyqxmd.com/read/30531196/biomarkers-of-drug-induced-kidney-toxicity
#1
Benjamin R Griffin, Sarah Faubel, Charles L Edelstein
Blood urea nitrogen (BUN) and serum creatinine are imperfect markers of kidney function because they are influenced by many renal and non-renal factors independent of kidney function. A biomarker that is released directly into the blood or urine by the kidney in response to injury may be a better early marker of drug-induced kidney toxicity than BUN and serum creatinine. Urine albumin and urine protein, as well as urinary markers kidney injury molecule-1 (KIM-1), β2-microglobulin (B2M), cystatin C, clusterin, and trefoil factor-3 (TFF-3) have been accepted by the Food and Drug Administration (FDA) and European Medicines Agency as highly sensitive and specific urinary biomarkers to monitor drug-induced kidney injury in preclinical studies and on a case-by-case basis in clinical trials...
December 10, 2018: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/30529997/sperm-and-seminal-plasma-proteomics-of-high-versus-low-fertility-holstein-bulls
#2
R K Kasimanickam, V R Kasimanickam, A Arangasamy, J P Kastelic
Sperm are highly specialized compartmentalized cells, with unique compositional, morphological and functional properties, including a plasma membrane that undergoes dynamic protein remodeling and surface modifications. Seminal plasma is a highly complex biological fluid containing proteins, amino acids, enzymes, fructose and other carbohydrates, lipids, major minerals and trace elements. Seminal plasma proteins are involved in regulation of osmotic pressure and pH of seminal plasma, transport of ions, lipid and hormones...
November 28, 2018: Theriogenology
https://www.readbyqxmd.com/read/30528350/eomesodermin-driven-il-10-production-in-effector-cd8-t-cells-promotes-a-memory-phenotype
#3
John Reiser, Kavitha Sadashivaiah, Aki Furusawa, Arnob Banerjee, Nevil Singh
CD8+ T cell differentiation is controlled by the transcription factors T-bet and Eomesodermin, in concert with the cytokines IL-2, IL-10 and IL-12. Among these pathways, the mechanisms by which T-box proteins and IL-10 interact to promote a memory T cell fate remain poorly understood. Here, we show that Eomes and IL-10 drive a central memory phenotype in murine CD8+ T cells. Eomes expression led to increased IL-10 expression by the effector CD8+ T cells themselves as well as an increase in the level of the lymph node homing selectin CD62L...
December 1, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/30526689/induced-pluripotent-stem-cell-derived-endothelial-progenitor-cells-attenuate-ischemic-acute-kidney-injury-and-cardiac-dysfunction
#4
Wen-Ching Shen, Yu-Hsiang Chou, Hsiang-Po Huang, Jenn-Feng Sheen, Shih-Chieh Hung, Hsin-Fu Chen
BACKGROUND: Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury (AKI), which is associated with high morbidity and mortality. AKI is a serious and costly medical condition. Effective therapy for AKI is an unmet clinical need, and molecular mechanisms underlying the interactions between an injured kidney and distant organs remain unclear. Therefore, novel therapeutic strategies should be developed. METHODS: We directed the differentiation of human induced pluripotent stem (iPS) cells into endothelial progenitor cells (iEPCs), which were then applied for treating mouse AKI...
December 10, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/30522767/the-proteome-microenvironment-determines-the-protective-effect-of-preconditioning-in-cisplatin-induced-acute-kidney-injury
#5
Martin R Späth, Malte P Bartram, Nicolàs Palacio-Escat, K Johanna R Hoyer, Cedric Debes, Fatih Demir, Christina B Schroeter, Amrei M Mandel, Franziska Grundmann, Giuliano Ciarimboli, Andreas Beyer, Jayachandran N Kizhakkedathu, Susanne Brodesser, Heike Göbel, Jan U Becker, Thomas Benzing, Bernhard Schermer, Martin Höhne, Volker Burst, Julio Saez-Rodriguez, Pitter F Huesgen, Roman-Ulrich Müller, Markus M Rinschen
Acute kidney injury (AKI) leads to significant morbidity and mortality; unfortunately, strategies to prevent or treat AKI are lacking. In recent years, several preconditioning protocols have been shown to be effective in inducing organ protection in rodent models. Here, we characterized two of these interventions-caloric restriction and hypoxic preconditioning-in a mouse model of cisplatin-induced AKI and investigated the underlying mechanisms by acquisition of multi-layered omic data (transcriptome, proteome, N-degradome) and functional parameters in the same animals...
November 29, 2018: Kidney International
https://www.readbyqxmd.com/read/30516423/klotho-deficiency-aggravates-sepsis-related-multiple-organ-dysfunction
#6
Lecticia Barbosa Jorge, Fernanda Oliveira Coelho, Talita Rojas Sanches, Denise M A C Malheiros, Leandro Ezaquiel de Souza, Fernando Dos Santos, Larissa de Sá Lima, Cristóforo Scavone, Maria Claudia Irigoyen, Makoto Kuro-O, Lucia Andrade
Sepsis-induced organ failure is characterized by a massive inflammatory response and oxidative stress. Acute kidney injury (AKI) occurs in approximately half of patients in septic shock, and the mortality associated with sepsis-induced AKI is unacceptably high. Klotho is a protein expressed by renal cells and has anti-senescence properties. Klotho has also been shown to protect the kidneys in ischemia-reperfusion injury and to have antioxidant properties. To analyze the role of Klotho in sepsis-related organ dysfunction and AKI, we used a cecal ligation and puncture (CLP) model of sepsis in heterozygous Klotho-haploinsufficient mice and their wild-type littermates (CLP-Kl+/- and CLP-WT mice, respectively)...
December 5, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/30511081/troxerutin-down-regulates-kim-1-modulates-p38-mapk-signaling-and-enhances-renal-regenerative-capacity-in-a-rat-model-of-gentamycin-induced-acute-kidney-injury
#7
Samir A Salama, Hany H Arab, Ibrahim A Maghrabi
Gentamycin is an aminoglycoside antibiotic that is widely employed for controlling Gram negative bacterial infections including that caused by the antibiotic-resistant Pseudomonas species. The clinical use of gentamycin is substantially limited by its side effects particularly acute kidney injury (AKI). The aim of the current study was to investigate the protective effect of the plant flavonoid troxerutin (150 mg kg-1 day-1 for 15 days) against gentamycin-induced AKI using Wistar rats as an experimental mammalian model...
December 4, 2018: Food & Function
https://www.readbyqxmd.com/read/30509215/short-term-dexamethasone-treatment-transiently-but-not-permanently-attenuates-fibrosis-after-acute-to-chronic-kidney-injury
#8
Lies Moonen, Hilde Geryl, Patrick C D'Haese, Benjamin A Vervaet
BACKGROUND: Acute kidney injury (AKI) is an underestimated, yet important, risk factor for the development of chronic kidney disease (CKD). Persistence of inflammation after a renal ischemic injury has been observed, both in experimental models and patients, and is thought to be an important mechanisms underlying progression of acute-to-chronic renal injury. Temporary suppression of inflammation immediately after AKI might therefore be a good first-line therapeutic strategy towards a better long term outcome...
December 3, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/30507607/targeting-protein-translation-to-prevent-septic-kidney-injury
#9
Sarah C Huen
The development of acute kidney injury (AKI) in patients with sepsis causes significant morbidity and mortality. The pathogenesis of AKI in sepsis is incompletely understood. In this issue of the JCI, Hato et al. investigate the renal translatome during bacterial sepsis and identify the global shutdown of renal protein translation mediated by the eukaryotic translation initiation factor 2-α kinase 2/eukaryotic translation initiation factor 2α (EIF2AK2/eIF2α) axis as a major pathway in mediating septic AKI...
December 3, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/30506859/deciphering-the-sumo-code-in-the-kidney
#10
REVIEW
Zhen Yang, Yuming Zhang, Shiren Sun
SUMOylation of proteins is an important regulatory element in modulating protein function and has been implicated in the pathogenesis of numerous human diseases such as cancers, neurodegenerative diseases, brain injuries, diabetes, and familial dilated cardiomyopathy. Growing evidence has pointed to a significant role of SUMO in kidney diseases such as DN, RCC, nephritis, AKI, hypertonic stress and nephrolithiasis. Recently, emerging studies in podocytes demonstrated that SUMO might have a protective role against podocyte apoptosis...
December 1, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/30503549/assessment-of-acute-kidney-injury-in-canine-parvovirus-infection-comparison-of-kidney-injury-biomarkers-with-routine-renal-functional-parameters
#11
M F van den Berg, J P Schoeman, P Defauw, Z Whitehead, A Breemersch, K Goethals, S Daminet, E Meyer
Dogs with naturally occurring canine parvovirus (CPV) infection are at risk of developing acute kidney injury (AKI) due to several factors, including severe dehydration, hypotension and sepsis. Serum creatinine (sCr) and serum urea are insensitive markers for the assessment of early kidney injury. Therefore, the aim of this study was to investigate potential kidney injury in dogs with CPV infection using both routine renal functional parameters and several kidney injury biomarkers. Twenty-two dogs with CPV infection were prospectively enrolled and compared with eight clinically healthy control dogs...
December 2018: Veterinary Journal
https://www.readbyqxmd.com/read/30502252/sirt3-inactivation-promotes-acute-kidney-injury-through-elevated-acetylation-of-sod2-and-p53
#12
Jie Ouyang, Zhenhua Zeng, Haihong Fang, Fei Li, Xinji Zhang, Wanlong Tan
BACKGROUND: The deactivation of SIRT3, a novel deacetylase located in mitochondria, can aggravate multiple organ dysfunction. However, the role of SIRT3 and its downstream targets in ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) remain unknown. MATERIALS AND METHODS: I/R was reproduced in a rat model using a clamp placed on the left and right renal pedicles for 40 min. The rats were intraperitoneally injected with either the vehicle or a selective SIRT3 inhibitor (3-TYP) and scarified at different time points (4, 8, and 24 h after I/R)...
January 2019: Journal of Surgical Research
https://www.readbyqxmd.com/read/30487750/sirt3-protects-against-acute-kidney-injury-via-ampk-mtor-regulated-autophagy
#13
Wenyu Zhao, Lei Zhang, Rui Chen, Hanlan Lu, Mingxing Sui, Youhua Zhu, Li Zeng
Acute kidney injury (AKI), which involves the loss of kidney function caused by damage to renal tubular cells, is an important public health concern. We previously showed that sirtuin (SIRT)3 protects the kidneys against mitochondrial damage by inhibiting the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome, attenuating oxidative stress, and downregulating proinflammatory cytokines. In this article, we investigated the role of autophagy, mediated by a mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), in the protective effect of SIRT3, against sepsis-induced AKI, in a mouse model of cecal ligation and puncture (CLP)...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/30483252/inflammasome-independent-role-of-nlrp3-mediates-mitochondrial-regulation-in-renal-injury
#14
Su-Mi Kim, Yang Gyun Kim, Dong-Jin Kim, Seon Hwa Park, Kyung-Hwan Jeong, Yu Ho Lee, Sung Jig Lim, Sang-Ho Lee, Ju-Young Moon
The NOD-like receptor family, pyrin domain containing-3 (NLRP3) inflammasome has been implicated in renal inflammation and fibrosis. However, the biological function of inflammasome-independent NLRP3 in non-immune cells is still unclear. We evaluated the role of inflammasome-independent NLRP3 in renal tubular cells and assessed the value of NLRP3 as a therapeutic target for acute kidney injury (AKI). Various renal tubular cell lines and primary cultured tubular cells from NLRP3 knockout (KO) mice were used for in vitro studies...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30480154/calcium-mobilization-is-responsible-for-thapsigargin-induced-epstein-barr-virus-lytic-reactivation-in-in-vitro-immortalized-lymphoblstoid-cell-lines
#15
Aki Hoji, Susie Xu, Holly Bilben, David T Rowe
The latent state is a critical component of all herpesvirus infections, and its regulation remains one of the most active areas of Epstein-Barr Virus (EBV) research. In particular, identifying environmental factors that trigger EBV reactivation into a virus-productive state has become a central goal in EBV latency research. Recently, a category of chemicals known as inducers of the endoplasmic reticulum unfolded protein response (UPR) have been shown to trigger EBV lytic reactivation in various established EBV-associated lymphoma cell lines...
November 2018: Heliyon
https://www.readbyqxmd.com/read/30461328/a-specific-immunoassay-for-detection-of-feline-kidney-injury-molecule-1
#16
S Karlyn Bland, Mary Ellen Clark, Olivier Côté, Dorothee Bienzle
OBJECTIVES: The aim of this study was to design and carry out a preliminary evaluation of a urine point-of-care test for kidney injury molecule 1( KIM-1) in healthy and diseased cats. METHODS: Part of the feline KIM-1 gene was amplified, ligated into a plasmid with a signal peptide and monomeric human IgGFc, and transfected into a mammalian cell line. Supernatant was purified and tested for the fusion protein by gel electrophoresis and Western blot. Mice were immunized three times with purified proteins, and hybridomas were generated from splenocytes...
November 21, 2018: Journal of Feline Medicine and Surgery
https://www.readbyqxmd.com/read/30450602/igfbp7-regulates-sepsis-induced-acute-kidney-injury-through-erk1-2-signaling
#17
Xiaolin Wang, Teng Ma, Xiaojian Wan, Yan Meng, Zhenzhen Zhao, Jinjun Bian, Rui Bao, Xiaoming Deng, Tao Yang
IGFBP7 as an early biomarker has been used to identify patients at risk of developing acute kidney injury (AKI). Nevertheless, its role in AKI remains obscure. The aim of our study is to determine the role and mechanism of IGFBP7 in lipopolysaccharide (LPS)-induced HK-2 cells in vitro and on sepsis-induced AKI by cecal ligation and puncture (CLP) in vivo. Here, we identified that IGFBP7 expression was increased in patients with AKI and HK-2 cells with LPS (1, 2, and 5 μg/mL) induction. HK-2 cells with LPS induction showed cell cycle arrest at G1-G0 phases and cell apoptosis and activated ERK1/2 parallel with the changes in the proteins belonging to the ERK1/2 pathway, including Cyclin D1, P21, Bax, and Bcl-2, which were inhibited by the IGFBP7 knockdown...
November 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/30441812/characterization-of-heterotrimeric-g-protein-%C3%AE-4-subunit-in-rice
#18
Sakura Matsuta, Aki Nishiyama, Genki Chaya, Takafumi Itoh, Kotaro Miura, Yukimoto Iwasaki
Heterotrimeric G proteins are the molecule switch that transmits information from external signals to intracellular target proteins in mammals and yeast cells. In higher plants, heterotrimeric G proteins regulate plant architecture. Rice harbors one canonical α subunit gene ( RGA1 ), four extra-large GTP-binding protein genes (XLGs), one canonical β-subunit gene ( RGB1 ), and five γ-subunit genes (tentatively designated RGG1 , RGG2 , RGG3 / GS3 / Mi / OsGGC1 , RGG4 / DEP1 / DN1 / qPE9-1 / OsGGC3 , and RGG5 / OsGGC2 ) as components of the heterotrimeric G protein complex...
November 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30441767/identification-of-heterotrimeric-g-protein-%C3%AE-3-subunit-in-rice-plasma-membrane
#19
Aki Nishiyama, Sakura Matsuta, Genki Chaya, Takafumi Itoh, Kotaro Miura, Yukimoto Iwasaki
Heterotrimeric G proteins are important molecules for regulating plant architecture and transmitting external signals to intracellular target proteins in higher plants and mammals. The rice genome contains one canonical α subunit gene ( RGA1 ), four extra-large GTP-binding protein genes (XLGs), one canonical β subunit gene (RGB1 ), and five γ subunit genes (tentatively named RGG1 , RGG2 , RGG3/GS3/Mi/OsGGC1 , RGG4/DEP1/DN1/OsGGC3 , and RGG5/OsGGC2 ). RGG1 encodes the canonical γ subunit; RGG2 encodes the plant-specific type of γ subunit with additional amino acid residues at the N-terminus; and the remaining three γ subunit genes encode the atypical γ subunits with cysteine abundance at the C-terminus...
November 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30429582/activation-of-%C3%AE-7-nicotinic-acetylcholine-receptor-ameliorates-zymosan-induced-acute-kidney-injury-in-balb-c-mice
#20
Sherehan M Ibrahim, Muhammad Y Al-Shorbagy, Dalaal M Abdallah, Hanan S El-Abhar
Zymosan, a natural compound, provokes acute peritonitis and multiple organ dysfunction that affects the kidney, beside other organs via exaggerated inflammatory response. The aim of the present study is to test the role of cholinergic anti-inflammatory pathway (CAP) in alleviating acute kidney injury (AKI) induced by zymosan in BALB/c mice, using galantamine, a cholinesterase inhibitor, known to act via α7 nicotinic acetylcholine receptor (α7 nAChR) to stimulate CAP. Galantamine verified its anti-inflammatory effect by elevating acetylcholine (ACh) level, while abating the interleukin-6/ janus kinase 2 (Y1007/1008)/ signal transducer and activator of transcription 3 (Y705) (IL-6/ pY(1007/1008)-JAK2/ pY705-STAT3) inflammatory axis, with a consequent inhibition in suppressor of cytokine signaling 3 (SOCS3)...
November 14, 2018: Scientific Reports
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